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Preparation and characterization of poly-DL-lactide-poly(ethylene glycol) microspheres containing lambda DNA

机译:含λDNA的聚-DL-丙交酯-聚(乙二醇)微球的制备与表征

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Polylacticle (PLA) and a block copolymer, poly-DL-lactide-poly(ethylene glycol) (PELA) were synthesized by bulk ring-opening polymerization initiated by stannous chloride. A linear DNA molecule, lambdaDNA, was used as the model DNA. PLA, PELA, lambdaDNA-loaded PLA and PELA microspheres were prepared by the solvent-extraction method based on the formation of multiple w(1)/o/w(2) emulsion. The particle-size distribution, surface morphology, and DNA loading characterized the microspheres. The mean diameter of lambdaDNA-loaded PELA microspheres was proved to be 3.5 mum. The integrity of the lambdaDNA molecules, after preparing the microspheres, was determined by agarose gel electrophoresis. The result suggested that most of the lambdaDNA molecules could retain their integrity after being encapsulated by PELA. The PELA microspheres could also prevent lambdaDNA from being degraded by DNase. The in vitro degradation and release of PLA, PELA, and lambdaDNA-loaded PELA microspheres were carried out in a pH 7.4 buffer solution at 37degreesC. Quantitatively, evaluating the molecular weight reduction, the mass loss, the particle-size changes, and the particle-size distribution changes also monitored the degree of degradation. The release profile was assessed by measurement of the amount of lambdaDNA present in the release medium at determined intervals. The degradation profiles of the PELA microspheres were quite different from those of the PLA microspheres. The introduction of the hydrophilic poly(ethylene glycol) domain in PLA and the presence of lambdaDNA within the microspheres exhibit the apparent influence on the degradation and release profiles. A biphasic release profile was proved, that is, an initial burst release during the first days, then a gradual release. It was demonstrated that the PELA microspheres could be used potentially as a controlled release-delivery system for lambdaDNA. (C) 2002 Wiley Periodicals, Inc. [References: 19]
机译:通过氯化亚锡引发的本体开环聚合反应合成了聚乳酸(PLA)和嵌段共聚物聚-DL-丙交酯-聚乙二醇(PELA)。线性DNA分子lambdaDNA被用作模型DNA。通过溶剂萃取法,基于多重w(1)/ o / w(2)乳液的形成,制备了PLA,PELA,装载了lambdaDNA的PLA和PELA微球。粒径分布,表面形态和DNA负载是微球的特征。负载lambdaDNA的PELA微球的平均直径为3.5微米。制备微球后,lambdaDNA分子的完整性通过琼脂糖凝胶电泳确定。结果表明,大多数lambdaDNA分子在被PELA包封后可以保留其完整性。 PELA微球还可以防止lambdaDNA被DNase降解。在37°C的pH 7.4缓冲溶液中进行PLA,PELA和装载lambdaDNA的PELA微球的体外降解和释放。定量地评估分子量降低,质量损失,粒度变化和粒度分布变化也监测了降解程度。通过以确定的间隔测量释放介质中存在的lambdaDNA的量来评估释放曲线。 PELA微球的降解曲线与PLA微球的降解曲线完全不同。 PLA中亲水性聚乙二醇域的引入以及微球中lambdaDNA的存在对降解和释放特性表现出明显的影响。证明了双相释放曲线,即在开始的几天中最初的突发释放,然后逐渐释放。结果表明,PELA微球可以潜在地用作lambdaDNA的控释-传递系统。 (C)2002 Wiley Periodicals,Inc. [参考:19]

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